The demands of present day living have placed a high premium on time. Voluntary sleep curtailment is endemic and many adults typically sleep an average of six hours per night. Observational data suggest that short sleep duration is associated with a greater likelihood of being obese. Low grade chronic sleep deprivation may constitute an important and potentially correctable behavioral factor in the alarming increase in obesity. There are no definitive experimental studies in humans showing whether sleep deprivation indeed contributes to increased energy intake and/or reduced energy expenditure. We propose a series of novel studies to investigate abnormalities in energy homeostasis imparted by sleep deprivation. These exploratory studies combine state-of-the-art techniques for monitoring sleep, food intake, energy expenditure and neuroendocrine energy regulation in humans. We will measure food intake, energy expenditure (basal metabolic rate, thermal effect of food, and non-exercise activity thermogenesis), and neurohormone levels in 24 healthy subjects with normal BMI (20-25 kg/m2). Twelve subjects (6 men and 6 women) will be randomized to sleep deprivation. After a 3 day baseline evaluation, these subjects will undergo 8 days of modest sleep deprivation followed by a 4 day recovery period. Measurements will be compared to those obtained in 12 subjects who are randomized to a control group, and are not sleep deprived. Sleep deprived and control subjects will be comparable for age and gender and will undergo similar monitoring and measurements in the Clinical Research Unit over the same duration. We will test the following hypotheses: 1. That sleep deprivation results in positive energy balance (increased caloric intake and decreased energy expenditure, as reflected by decreased non-exercise activity thermogenesis). 2. That dysregulation of appetite and energy expenditure is associated with changes in molecules controlling appetite and metabolism. 3. That changes associated with 8 days of modest sleep deprivation resolve, at least in part, over a 4 day recovery period. This exploratory application builds on established research programs addressing first, neuroendocrine mechanisms in sleep and obesity, and second, the regulation of energy intake and energy expenditure in humans. These studies will provide novel and important insights into whether sleep deprivation promotes increased food intake and/or reduced activity levels, and into the potential role of molecules that regulate appetite and metabolism. PUBLIC HEALTH RELEVANCE: We propose to examine whether two weeks of modest sleep restriction results in increased food intake and decreased energy expenditure, thus potentially predisposing to obesity. These findings will help explain whether the reduced sleep duration in the general population may be contributing to the current epidemic of obesity, and suggest novel strategies for weight control.